The compound of formula 1 is known from the prior art and was first disclosed in WO98/37075. It is a potent thrombin inhibitor which can be used for example for the post-operative prevention of deep vein thromboses and in stroke prevention, particularly for preventing strokes in patients with atrial fibrillation. WO 03/074056 discloses the methanesulphonic acid addition salt of dabigatran-etexilate (ie: dabigatran etexilate methansulphonate) to be particularly useful.
The compound is usually administered orally. In particular, so-called pellet formulations may be used, as disclosed for example in WO 03/074056. These formulations are compositions, in which an active substance layer containing binder and optionally separating agent and surrounding a core material is applied to the substantially spherical core material, which consists of or contains a pharmaceutically acceptable organic acid. The core layer and the active substance layer are separated from one another by a so-called isolating layer. The schematic structure of an active substance formulation of this kind is shown in FIG. 1 of WO 03/074056.
The present invention relates to a process that can be used on an industrial scale for preparing active substance pellets containing dabigatran, which allows the formulation to be manufactured on a large scale. A further aim of the invention is to provide a process which allows the formulation to be manufactured with a reproducible quality.
According to WO 05/028468 the methansulphonic acid addition salt of dabigatran etexilate exists in different polymorphic forms. It is another aim of the invention to provide for a manufacturing process which allows the manufacture of a pharmaceutical formulation that contains only one polymorphic form of the active ingredient dabigatran etexilat methansulphonate.